M. Selman Yildirim

Evaluation of chromosome 8 and 11 aneuploidies in washings and biopsy materials of bladder transitional cell carcinoma

We compared chromosome 8 and 11 aneuploidies on bladder biopsy tumor tissues and bladder washing samples of transitional cell carcinoma (TCC) and their relationship to tumor malignancy. Interphase fluorescence in situ hybridization (FISH) was applied to nuclei of washing material and biopsy samples of 17 patients with TCC. Incidence of cells having aneuploidy was clearly nonrandom from patient to patient. There was no significant difference in the incidence of aneuploid frequency for chromosomes 8 and 11 between biopsies of bladder tumors and bladder washing samples (P > 0.05). For chromosome 8, incidence of disomic cells (having two signals) in grade III tumors was significantly lower than in grade II tumors of both washing samples (P = 0.004) and biopsy materials (P = 0.005), indicating a high frequency of aneuploidy. The incidence of nuclei with four or more than four signals of chromosome 8 was significantly higher in grade III tumors than in grade II tumors in washing samples (P = 0.031 and 0.003, respectively). Similarly, in biopsy material, the incidence of nuclei with more than four signals of chromosome 8 was significantly higher in grade III tumors than in grade II tumors (P = 0.004). For chromosome 11, in both washing samples and biopsy materials, the incidence of disomic cells (having two signals) in grade III tumors was significantly lower than that detected in grade II tumors (P = 0.031 and 0.014, respectively), indicating a high frequency of aneuploidy. In biopsy materials, the incidence of nuclei with three or four signals was significantly higher than that in grade II tumors (P = 0.014 and 0.012, respectively). These findings suggest that FISH analysis of bladder washing samples can be effectively detected as genetic changes of bladder tumors. It might predict genetic progression of these tumors, which might be related to tumor stage, because higher stages of tumors showed a higher incidence of aneuploidies of chromosomes 8 and 11.

Whole exome sequencing identifies three novel mutations in ANTXR1 in families with GAPO syndrome

GAPO syndrome (OMIM#230740) is the acronym for growth retardation, alopecia, pseudoanodontia, and optic atrophy. About 35 cases have been reported, making it among one of the rarest recessive conditions. Distinctive craniofacial features including alopecia, rarefaction of eyebrows and eyelashes, frontal bossing, high forehead, mid‐facial hypoplasia, hypertelorism, and thickened eyelids and lips make GAPO syndrome a clinically recognizable phenotype. While this genomic study was in progress mutations in ANTXR1 were reported to cause GAPO syndrome. In our study we performed whole exome sequencing (WES) for five affected individuals from three Turkish kindreds segregating the GAPO trait. Exome sequencing analysis identified three novel homozygous mutations including; one frame‐shift (c.1220_1221insT; p.Ala408Cysfs*2), one splice site (c.411A>G; p.Gln137Gln), and one non‐synonymous (c.1150G>A; p.Gly384Ser) mutation in the ANTXR1 gene. Our studies expand the allelic spectrum in this rare condition and potentially provide insight into the role of ANTXR1 in the regulation of the extracellular matrix.

A girl with metopic synostosis and trisomy 13 mosaicism: Case report and review of the literature

Trisomy 13, or Patau syndrome is a rare chromosomal disorder characterized by a triad of cleft lip and palate, postaxial polydactyly and microcephaly. Complete, partial, or mosaic forms of the disorder can occur. Mosaic trisomy 13 is very rare, it occurs in only 5% of all patients with trisomy 13 phenotype. Metopic synostosis (MS) is premature fusion of the metopic suture, which is part of the frontal suture. It results in a V‐shaped abnormality at the front of the skull. MS may occur in a syndromic or nonsyndromic form. We report on a 24‐day‐old girl with hypotonia, MS, trigonocephaly, capillary hemangioma, hypotelorism, upward slanting palpebral fissures, epicanthal folds, small nose with anteverted nares, high palate, ankyloglossia, long philtrum, low‐set ears, short neck, postaxial polydactyly of both hands and feet and congenital heart defect. Cytogenetic analysis demonstrated trisomy 13 mosaicism; 46,XX[58]/47,XX,+13[42]. Although MS has been previously reported in complete and partial forms of trisomy 13, it has not been reported in mosaic form of trisomy 13. Our report supports the evidence that trisomy 13 causes MS. It also emphasizes the need for cytogenetic investigations in patients presenting with MS and multiple congenital anomalies for providing accurate diagnosis, genetic counseling, and prenatal diagnosis.

Recurrent proximal 18p monosomy and 18q trisomy in a family due to a pericentric inversion

Here, we report on a family with pericentric inversion of chromosome 18 [inv(18)(p11.2q21)] and two recombinants with a duplication of q21 → qter and a deletion of p11.2 → pter regions in a four‐generation family. This chromosomal abnormality was inherited in our first patient from the father, while it was transmitted to the second patient from the mother. Array‐CGH analysis were used to better characterize duplicated and deleted chromosomal regions and showed no genomic copy number variation (CNV) differences between these two relatives. We discussed genotype‐phenotype correlations including previously reported.

Micronucleus frequency in acquired middle ear cholesteatoma

Objective—To determine the micronucleus (MN) frequency of acquired cholesteatoma tissue using an MN assay. Material and Methods—Eighteen patients were diagnosed as having chronic otitis media with acquired cholesteatoma and were divided into primary and secondary acquired cholesteatoma groups. Cholesteatoma tissue and normal tissue specimens from the external ear canal skin were taken from the patients during surgical operations. MN frequencies of cholesteatoma and control samples were determined according to standard criteria. Results—The MN frequencies of the cholesteatoma and control tissues were 0.54%±0.31% and 0.24%±0.11%, respectively (p<0.01). MN frequencies for the primary and secondary acquired cholesteatoma groups were 0.63%±0.36% and 0.46%±0.26%, respectively (p>0.05). MN frequencies in cholesteatoma patients without and with complications were 0.42%±0.19% and 0.85%±0.37%, respectively (p<0.05). Conclusion—MN frequencies were found to be increased in cholesteatoma tissues when compared with external ear canal skin. The MN frequency in five cases with complications was higher than in cases without complications. These results indicate that there could be associations between MN frequency and acquired cholesteatoma and between MN frequency and complications.

Micronuclei frequencies in lymphocytes and cervical cells of women with polycystic ovarian syndrome

Objective: The aim of this study was to determine micronucleus (MN) frequencies in exfoliated cervical cells and peripheral blood lymphocytes of women with polycystic ovarian syndrome (PCOS). Materials and Methods: Fifteen patients with PCOS and 11 healthy control patients were included in the study. Cervical smears and peripheral blood were collected from all patients. Specimens were analyzed for MN frequencies and compared between the groups. In addition to MN, other nuclear anomalies connected with both genotoxicity and cytotoxicity were evaluated. Results: The MN frequencies in cervical smear and peripheral blood lymphocytes were compared in patients with PCOS and normal controls. There was no statistically significant difference between the groups regarding micronucleus frequency in peripheral blood lymphocytes (p=0.239). The mean MN scores in exfoliated cervical cells of patients with PCOS and normal controls were 1.19±0.57 and 0.74±0.34, respectively. The difference regarding micronucleus frequencies in cervical cells was statistically significant between the groups (p=0.032). Conclusion: Although study group is small, our study results support that there is an increased micronucleus frequency in cervical exfoliated cells of PCOS patients; this is a determinant of genetic hazard in the disease.